Many recombinant proteins are produced in a variety of host organisms. Most proteins can be expressed in their native form in eukaryotic hosts such as CHO cells. Animal cell culture generally requires prolonged growing times to achieve maximum cell density and often require expensive media containing growth components that may interfere with the recovery of the desired protein. Bacterial host expression systems provide a cost-effective alternative to the manufacturing scale production of recombinant proteins. Recombinant proteins overexpressed in Escherichia coli are often accumulated as insoluble particles called inclusion bodies. Since proteins in inclusion bodies are usually inactive, they must be solubilized by a denaturing agent and refolded to recover their active form. When producing proteins, it is generally desirable to obtain a high refolding efficiency and high throughput at high protein concentrations.
There is a need for new and more effective methods of folding and/or recovering recombinant proteins from a host cell culture, e.g., for the efficient and economical production of recombinant proteins in bacterial cell culture.